Novel polymers with hydroxyl acid blocks

ABSTRACT

The present invention relates polymers comprising non-degradable blocks and degradable blocks and methods of manufacturing such polymers.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of, and priority to, U.S.Provisional Patent Application Ser. No. 61/095,541, filed on Sep. 9,2008, the entire disclosure of which is hereby incorporated by referencein its entirety.

FIELD OF THE INVENTION

The present invention relates to the preparation of modified polymers bychemically incorporating a compositional modifier into a polymer chainto produce the modified polymer. More particularly, the inventionrelates to the preparation of condensation type copolyesters by joiningshort length polyester or polyester oligomers with a modifier whichcontains hydroxyl acids blocks.

BACKGROUND OF THE INVENTION

Condensation polymers such as thermoplastic polyesters, polycarbonates,and polyamides have many desirable physical and chemical attributes thatmake them useful for a wide variety of molded, fiber, and filmapplications. However, for specific applications, these polymers alsoexhibit limitations that should be minimized or eliminated. To overcomethese limitations, polymers are frequently made containing one or moreadditives or comonomers depending upon the desired end use of thepolymer. One of the most common thermoplastic polyester polymers ispolyethylene terephthalate (PET).

PET polymer is used extensively in the packaging industry, especially inthe production of bottles for carbonated and non-carbonated beverages.In the carbonated beverage industry, concerns include the rate of carbondioxide escape from the container, taste deterioration of the contentsdue to degradation by light, and extraction of additives added eitherduring melt polymerization or subsequent melt processing that isrequired to fabricate the container. To overcome these problems, PETresins are often modified by incorporating unique comonomers into thepolymer backbone thus producing a wide variety of PET copolyesters. Forexample, 2,6-naphthalenedicarboxylate (2,6-NDC) is coplymerized withethylene glycol (EG) and terephthalic acid (TPA), propylene glycol iscoplymerized with ethylene glycol (EG) and terephthalic acid (TPA) (U.S.Pat. No. 6,313,235), and isophthalic acid (IPA) is coplymerized withethylene glycol (EG) and terephthalic acid (TPA) (U.S. Pat. Nos. 7,297,721, 6,489,434, and 6,913,806).

Condensation polymers may be degraded by hydrolysis with catalyst ofacid, or base. The rate of depolymerization depends upon the structureof the polymers. Poly(hydroxyl acids), such as poly glycolic acid orpoly lactic acid or copolymers of glycolic acid and lactic acid areeasily hydrolyzed at mild conditions, even at pH 7 and room temperaturein several months. Therefore, poly(hydroxyl acids) have wideapplications based on their degradability, such as in medical devicesand drug delivery system. On the other hand, polyethylene terephthalate(PET) hydrolyzes very slowly at mild conditions. To decompose such kindof polyester will require high temperature and high pressure throughreaction with methanol, ethylene glycol or ammonia/glycol, which allinvolves organic solvents. PET and its derivatives have also wideapplications based on their non-degradability and mechanical strength,such as fibers, packaging bottles and films.

Although there are many attempts to modify condensation polymers forextension of their application as described above, no attempts have beenreported to incorporate degradable blocks of polyester intonon-degradable condensation polyester in which the degradable blocks areuniformly distributed in the polymer chains.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides a polymer comprisingnon-degradable blocks and degradable blocks. In some embodiments, thepolymer has a structure of Formulae (Ia) or (Ib):

wherein t, m, p, q, r are integers other than zero, n is integersincludes zero, R, R₁, R₂, R₃, R₄, R″ are members independently selectedin each structural units from H, substituted or unsubstituted alkyl,substituted or unsubstituted heteroalkyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted heterocycloalkyl, substitutedor unsubstituted aryl and substituted or unsubstituted heteroaryl,substituted or unsubstituted alkoxy, ester, nitro, amine, amide, orthiol. In some embodiments, the R, R₁, R₂, R₃, R₄, R″ are independentlyC₁-C₁₀ alkyls.

In some embodiments, the degradable blocks has a structure according toFormula (III)

wherein t, m, n are integers other than zero, X is Cl, Br, I, NH₂—, HO—,R′OCO—C₆H₄—COO— (where R′ is H, CH₃, C₂H₅ or any other alkyls) or otherpolymer chains and R, R₁, R₂ are members independently selected in eachstructural units from H, substituted or unsubstituted alkyl, substitutedor unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heteroaryl,substituted or unsubstituted alkoxy, ester, nitro, amine, amide, orthiol.

In some embodiments, the degradable blocks has a structure according toFormula (IV):

wherein t, m, n are integers, R, R₁, R₂, are alkyls (CH₃, C₂H₅ . . . ),R″ is any substitute groups, and R′ is H or alkyls.

In another aspect, the present invention provides a degradable segmentaccording to Formula (III):

wherein t, m, n are integers other than zero, X is Cl, Br, I, NH₂—, HO—,R′OCO—C₆H₄—COO— (where R′ is H, CH₃, C₂H₅ or any other alkyls) or otherpolymer chains and R, R₁, R₂ are members independently selected in eachstructural units from H, substituted or unsubstituted alkyl, substitutedor unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heteroaryl,substituted or unsubstituted alkoxy, ester, nitro, amine, amide, orthiol. In some embodiments the degradable segment is made according toScheme Ia:

In another aspect, the present invention provides a degradable segmentaccording to Formula (IV):

wherein t, m, n are integers, R, R₁, R₂ are alkyls (CH₃, C₂H₅ . . . ),R″ is any substitute groups, and R′ is H or alkyls. In some embodimentsthe degradable segment is made according to Scheme Ib:

In another aspect, the present invention provides a method of making apolymer comprising degradable blocks and non-degradable blocks, saidmethod comprises the steps of: (a) synthesizing degradable hydroxylacids blocks; (b) polymerizing non degradable polymer monomer or prepolymer with degradable hydroxyl acids blocks to form said polymers in asolution polymerization process or melting polymerization process.

In another aspect, the present invention provides a method of making apolymer comprising degradable blocks and non-degradable blocks, saidmethod comprises the steps of (a) synthesizing degradable hydroxyl acidsblocks; (b) synthesizing non-degradable polymers; and (c) joining saidnon-degradable blocks with and said degradable polymers in a solutionpolymerization process or melting polymerization process.

In some embodiments of the method provided herein, the polymer has thestructure according to Formulae (Ia) or (Ib):

wherein t, m, n, p, q are integers other than zero, R, R₁, R₂, R₃, R₄,R″ are members independently selected in each structural units from H,substituted or unsubstituted alkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted heterocycloalkyl, substituted or unsubstituted aryl andsubstituted or unsubstituted heteroaryl, substituted or unsubstitutedalkoxy, ester, nitro, amine, amide, or thiol.

In some embodiments of the method provided herein the degradable blockshave the structure according to Formula (II):

wherein t, m are integers; X is Cl, Br, I, NH₂—, or HO—, R′OCO—C₆H₄—COO—(where R′ is H, CH₃, C₂H₅ or any other alkyls) and R is H, substitutedor unsubstituted alkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedheterocycloalkyl, substituted or unsubstituted aryl and substituted orunsubstituted heteroaryl, substituted or unsubstituted alkoxy, ester,nitro, amine, amide, or thiol, or Formula (III):

wherein t, m, n are integers other than zero, X is Cl, Br, I, NH₂—, HO—,R′OCO—C₆H₄—COO— (where R′ is H, CH₃, C₂H₅ or any other alkyls), and R,R₁, R₂ are members independently selected in each structural units fromH, substituted or unsubstituted alkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted heterocycloalkyl, substituted or unsubstituted aryl andsubstituted or unsubstituted heteroaryl, substituted or unsubstitutedalkoxy, ester, nitro, amine, amide, or thiol.

In some embodiments of the method provided herein, the degradable blocksare diol. In some embodiments, the non-degradable blocks are esters. Insome embodiments, the degradable blocks have the structure according toFormula (IV):

wherein t, m, n are integers, X is Cl, Br, I, NH₂—, HO—, R is alkyls(CH₃, C₂H₅ . . . ), R″ is any substitute groups, and R′ is H or alkyls.

In some embodiments of the method provided herein, the step (a) iscarried out according to Scheme (Ia):

In some embodiments of the method provided herein, the step (a) iscarried out according to Scheme (II):

In some embodiments of the method provided herein, the step (c) iscarried out according to Scheme (IV):

In some embodiments of the method provided herein, the degradable andnon-degradable blocks comprise carbonyl chloride ends and said carbonylchloride are converted into carboxylic acid before said step (c).

DETAILED DESCRIPTION OF THE INVENTION I. Definitions and Abbreviations

Unless defined otherwise, all technical and scientific terms used hereingenerally have the same meaning as commonly understood by one ofordinary skill in the art to which this invention belongs. Generally,the nomenclature used herein and the laboratory procedures in cellculture, molecular genetics, organic chemistry and nucleic acidchemistry and hybridization are those well known and commonly employedin the art. Standard techniques are used for nucleic acid and peptidesynthesis. The techniques and procedures are generally performedaccording to conventional methods in the art and various generalreferences, which are provided throughout this document. Thenomenclature used herein and the laboratory procedures in analyticalchemistry, and organic synthetic described below are those well knownand commonly employed in the art. Standard techniques, or modificationsthereof, are used for chemical syntheses and chemical analyses.

The term “alkyl,” by itself or as part of another substituent, means,unless otherwise stated, a straight or branched chain, or cyclichydrocarbon radical, or combination thereof, which may be fullysaturated, mono- or polyunsaturated and can include di- and multivalentradicals, having the number of carbon atoms designated (i.e. C₁-C₁₀means one to ten carbons). Examples of saturated hydrocarbon radicalsinclude, but are not limited to, groups such as methyl, ethyl, n-propyl,isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl,(cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of forexample, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. Anunsaturated alkyl group is one having one or more double bonds or triplebonds. Examples of unsaturated alkyl groups include, but are not limitedto, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl),2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl,3-butynyl, and the higher homologs and isomers. The term “alkyl,” unlessotherwise noted, is also meant to include those derivatives of alkyldefined in more detail below, such as “heteroalkyl.” Alkyl groups, whichare limited to hydrocarbon groups, arc termed “homoalkyl”.

The term “alkylene” by itself or as part of another substituent means adivalent radical derived from an alkane, as exemplified, but notlimited, by —CH₂CH₂CH₂CH₂—, and further includes those groups describedbelow as “heteroalkylene.” Typically, an alkyl (or alkylene) group willhave from 1 to 24 carbon atoms, with those groups having 10 or fewercarbon atoms being preferred in the present invention. A “lower alkyl”or “lower alkylene” is a shorter chain alkyl or alkylene group,generally having eight or fewer carbon atoms.

The terms “alkoxy,” “alkylamino” and “alkylthio” (or thioalkoxy) areused in their conventional sense, and refer to those alkyl groupsattached to the remainder of the molecule via an oxygen atom, an aminogroup, or a sulfur atom, respectively.

The term “heteroalkyl,” by itself or in combination with another term,means, unless otherwise stated, a stable straight or branched chain, orcyclic hydrocarbon radical, or combinations thereof, consisting of thestated number of carbon atoms and at least one heteroatom selected fromthe group consisting of O, N, Si and S, and wherein the nitrogen andsulfur atoms may optionally be oxidized and the nitrogen heteroatom mayoptionally be quaternized. The heteroatom(s) O, N and S and Si may beplaced at any interior position of the heteroalkyl group or at theposition at which the alkyl group is attached to the remainder of themolecule. Examples include, but are not limited to, —CH₂—CH₂—O—CH₃,—CH₂—CH₂—NH—CH₃, —CH₂—CH₂—N(CH₃)—CH₃, —CH₂—S—CH₂—CH₃, —CH₂—CH₂,—S(O)—CH₃, —CH₂—CH₂—S(O)₂—CH₃, —CH═CH—O—CH₃, —Si(CH₃)₃, —CH₂—CH═N—OCH₃,and —CH═CH—N(CH₃)—CH₃. Up to two heteroatoms may be consecutive, suchas, for example, —CH₂—NH—OCH₃ and —CH₂—O—Si(CH₃)₃. Similarly, the term“heteroalkylene” by itself or as part of another substituent means adivalent radical derived from heteroalkyl, as exemplified, but notlimited by, —CH₂—CH₂—S—CH₂—CH₂— and —CH₂—S—CH₂—CH₂—NH—CH₂—. Forheteroalkylene groups, heteroatoms can also occupy either or both of thechain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino,alkylenediamino, and the like). Still further, for alkylene andheteroalkylene linking groups, no orientation of the linking group isimplied by the direction in which the formula of the linking group iswritten. For example, the formula —C(O)₂R′— represents both —C(O)₂R′—and —R′C(O)₂—.

In general, an “acyl substituent” is also selected from the group setforth above. As used herein, the term “acyl substituent” refers togroups attached to, and fulfilling the valence of a carbonyl carbon thatis either directly or indirectly attached to the polycyclic nucleus ofthe compounds of the present invention.

The terms “cycloalkyl” and “heterocycloalkyl”, by themselves or incombination with other terms, represent, unless otherwise stated, cyclicversions of “alkyl” and “heteroalkyl”, respectively. Additionally, forheterocycloalkyl, a heteroatom can occupy the position at which theheterocycle is attached to the remainder of the molecule. Examples ofcycloalkyl include, but are not limited to, cyclopentyl, cyclohexyl,1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. Examples ofheterocycloalkyl include, but are not limited to,1-(1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl,3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl,tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl,1-piperazinyl, 2-piperazinyl, and the like.

The terms “halo” or “halogen,” by themselves or as part of anothersubstituent, mean, unless otherwise stated, a fluorine, chlorine,bromine, or iodine atom. Additionally, terms such as “haloalkyl,” aremeant to include monohaloalkyl and polyhaloalkyl. For example, the term“halo(C₁-C₄)alkyl” is mean to include, but not be limited to,trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, andthe like.

The term “aryl” means, unless otherwise stated, a polyunsaturated,aromatic, hydrocarbon substituent, which can be a single ring ormultiple rings (preferably from 1 to 3 rings), which are fused togetheror linked covalently. The term “heteroaryl” refers to aryl groups (orrings) that contain from one to four heteroatoms selected from N, O, andS, wherein the nitrogen and sulfur atoms are optionally oxidized, andthe nitrogen atom(s) are optionally quaternized. A heteroaryl group canbe attached to the remainder of the molecule through a heteroatom.Non-limiting examples of aryl and heteroaryl groups include phenyl,1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl,3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl,4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl,5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 2-furyl, 3-furyl, 2-thienyl,3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl,5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl,5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and6-quinolyl. Substituents for each of the above noted aryl and heteroarylring systems are selected from the group of acceptable substituentsdescribed below.

For brevity, the term “aryl” when used in combination with other terms(e.g., aryloxy, arylthioxy, arylalkyl) includes both aryl and heteroarylrings as defined above. Thus, the term “arylalkyl” is meant to includethose radicals in which an aryl group is attached to an alkyl group(e.g., benzyl, phenethyl, pyridylmethyl and the like) including thosealkyl groups in which a carbon atom (e.g., a methylene group) has beenreplaced by, for example, an oxygen atom (e.g., phenoxymethyl,2-pyridyloxymethyl, 3-(1-naphthyloxy)propyl, and the like).

Each of the above terms (e.g., “alkyl,” “heteroalkyl,” “aryl” and“heteroaryl”) include both substituted and unsubstituted forms of theindicated radical. Preferred substituents for each type of radical areprovided below.

Substituents for the alkyl, and heteroalkyl radicals (including thosegroups often referred to as alkylene, alkenyl, heteroalkylene,heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, andheterocycloalkenyl) are generally referred to as “alkyl substituents”and “heteroalkyl substituents,” respectively, and they can be one ormore of a variety of groups selected from, but not limited to: —OR′, ═O,═NR′, ═N—OR′, —NR′R″, —SR═, -halogen, —SiR′R″R′″, —OC(O)R′, —C(O)R′,—CO₂R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O)₂R′,—NR—C(NR′R″R′″)═NR″″, —NR—C(NR′R″)═NR′″, —S(O)R′, —S(O)₂R′, —S(O)₂NR′R″,—NRSO₂R′, —CN and —NO₂ in a number ranging from zero to (2m′+1), wherem′ is the total number of carbon atoms in such radical. R′, R″, R′″ andR″″ each preferably independently refer to hydrogen, substituted orunsubstituted heteroalkyl, substituted or unsubstituted aryl, e.g., arylsubstituted with 1-3 halogens, substituted or unsubstituted alkyl,alkoxy or thioalkoxy groups, or arylalkyl groups. When a compound of theinvention includes more than one R group, for example, each of the Rgroups is independently selected as are each R′, R″, R′″ and R″″ groupswhen more than one of these groups is present. When R′ and R″ areattached to the same nitrogen atom, they can be combined with thenitrogen atom to form a 5-, 6-, or 7-membered ring. For example, —NR′R″is meant to include, but not be limited to, 1-pyrrolidinyl and4-morpholinyl. From the above discussion of substituents, one of skillin the art will understand that the term “alkyl” is meant to includegroups including carbon atoms bound to groups other than hydrogengroups, such as haloalkyl (e.g., —CF₃ and —CH₂CF₃) and acyl (e.g.,—C(O)CH₃, —C(O)CF₃, —C(O)CH₂OCH₃, and the like).

Similar to the substituents described for the alkyl radical, the arylsubstituents and heteroaryl substituents are generally referred to as“aryl substituents” and “heteroaryl substituents,” respectively and arevaried and selected from, for example: halogen, —OR′, ═O, ═NR═, ═N—OR′,—NR′R″, —SR′, -halogen, —SiR′R″R′″, —OC(O)R′, —C(O)R′, —CO₂R′, —CONR′R″,—OC(O)NR′R″, —NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O)₂R′,—NR—C(NR′R″)═NR′″, —S(O)R′, —S(O)₂R′, —S(O)₂NR′R″, —NRSO₂R′, —CN and—NO₂, —R′, —N₃, —CH(Ph)₂, fluoro(C₁-C₄)alkoxy, and fluoro(C₁-C₄)alkyl,in a number ranging from zero to the total number of open valences onthe aromatic ring system; and where R′, R″, R′″ and R″″ are preferablyindependently selected from hydrogen, (C₁-C₈)alkyl and heteroalkyl,unsubstituted aryl and heteroaryl, (unsubstituted aryl)-(C₁-C₄)alkyl,and (unsubstituted aryl)oxy-(C₁-C₄)alkyl. When a compound of theinvention includes more than one R group, for example, each of the Rgroups is independently selected as are each R′, R″, R′″ and R″″ groupswhen more than one of these groups is present.

Two of the aryl substituents on adjacent atoms of the aryl or heteroarylring may optionally be replaced with a substituent of the formula-T-C(O)—(CRR′)_(q)—U—, wherein T and U are independently —NR—, —O—,—CRR′— or a single bond, and q is an integer of from 0 to 3.Alternatively, two of the substituents on adjacent atoms of the aryl orheteroaryl ring may optionally be replaced with a substituent of theformula -A-(CH₂)_(r)—B—, wherein A and B are independently —CRR′—, —O—,—NR—, —S—, —S(O)—, —S(O)₂—, —S(O)₂NR′— or a single bond, and r is aninteger of from 1 to 4. One of the single bonds of the new ring soformed may optionally be replaced with a double bond. Alternatively, twoof the substituents on adjacent atoms of the aryl or heteroaryl ring mayoptionally be replaced with a substituent of the formula—(CRR′)_(s)—X—(CR″R′″)_(d)—, where s and d are independently integers offrom 0 to 3, and X is —O—, —NR′—, —S—, —S(O)—, —S(O)₂—, or —S(O)₂NR′—.The substituents R, R′, R″ and R′″ are preferably independently selectedfrom hydrogen or substituted or unsubstituted (C₁-C₆) alkyl.

As used herein, the term “heteroatom” includes oxygen (O), nitrogen (N),sulfur (S), phosphorus (P) and silicon (Si).

II. The Compositions

In one aspect, the present invention provides condensation polymerscomprising degradable blocks of short chain length of poly hydroxylacids as joints of non-degradable polymer chains. In general, suchpolymers retains the mechanical strength of non-degradable blocks (themajor blocks of the polymer) but are easily degraded at their degradableblocks (the location of joints) and therefore the long chain polymerswill be degraded back to non-degradable short chains.

In some embodiments, the present invention provides degradable blocks ordegradable segments having the structure according to Formula (III):

wherein t, m, n are integers; X is Cl, Br, I, NH₂—, HO—, R′OCO—C₆H₄—COO—(where R′ is H, CH₃, C₂H₅ or any other alkyls) or other polymer chains,and R₁, R₂ are members independently selected in each structural unitsfrom H, substituted or unsubstituted alkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted heterocycloalkyl, substituted or unsubstituted aryl andsubstituted or unsubstituted heteroaryl, substituted or unsubstitutedalkoxy, ester, nitro, amine, amide, or thiol. In some embodiments, X isremoved when incorporated into polymers.

In some embodiments, the present invention provides degradable blocks ordegradable segments having the structure according to Formula (IV):

wherein t, m, n are integers; R, R₁, R₂ are alkyls (CH₃, C₂H₅ . . . );R′ is H or alkyls (CH₃, C₂H₅ . . . ); R″ is any substitute groups; andR′ is H, substituted or unsubstituted alkyl, substituted orunsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heteroaryl,substituted or unsubstituted alkoxy, ester, nitro, amine, amide, orthiol.

In some embodiments, the non-degradable blocks are polyester (excludethe polyhydroxyl acids, which are degradable), with functional groups toreact with degradable short chains. By “non-degradable” herein is meantthat the rate of hydrolysis is much slower then that of polyhydroxyacids, rather than absolutely no degradation.

In one aspect, the present invention provides non-degradable polymerswith degradable blocks. These polymers comprise of both degradableblocks and non-degradable blocks such as Formulae (Ia) and (IIb):

wherein t, m, n, p, q are integers; R, R₁, R₂, R₃, R₄, R″ are membersindependently selected in each structural units from H, substituted orunsubstituted alkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedheterocycloalkyl, substituted or unsubstituted aryl and substituted orunsubstituted heteroaryl, substituted or unsubstituted alkoxy, ester,nitro, amine, amide, or thiol.

In some embodiments, R, R₁, R₂, R″ are independently C₁ to C₁₀ alkyls.

In some embodiments, the degradable blocks are short chain polyhydroxyacids with functional groups at both ends to react with nondegradable-blocks.

In some embodiments, the polymers comprise degradable blocks accordingto Formulae (IIIa):

wherein t, m, n are integers; and R, R₁, R₂ are members independentlyselected in each structural units from H, substituted or unsubstitutedalkyl, substituted or unsubstituted heteroalkyl, substituted orunsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl,substituted or unsubstituted aryl and substituted or unsubstitutedheteroaryl, substituted or unsubstituted alkoxy, ester, nitro, amine,amide, or thiol.

In some embodiments, the polymers comprise degradable blocks accordingto Formulae (IV):

wherein t, m, n are integers; R, R₁, R₂, are alkyls (CH₃, C₂H₅ . . . );R″ is any substitute groups; and R′ is H, substituted or unsubstitutedalkyl, substituted or unsubstituted heteroalkyl, substituted orunsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl,substituted or unsubstituted aryl and substituted or unsubstitutedheteroaryl, substituted or unsubstituted alkoxy, ester, nitro, amine,amide, or thiol.

The ratio between the non-degradable blocks and the degradable blocks inthe polymers can vary. In some embodiments, the polymers comprisesnon-degradable blocks as major components (from 50% to 100% weightpercentage) and degradable blocks as minor components (from 0% to 50%weight percentage).

III. Method of Making

In another aspect, the present invention provides methods ofmanufacturing polymers. The method of manufacturing polymers withdegradable blocks in present invention comprises three major modules:(a) synthesis of degradable hydroxyl acids blocks, (b) synthesis ofnon-degradable polymers, and (c) joining both degradable blocks and nondegradable polymers together.

(a). Synthesis of Degradable Hydroxyl Acids Blocks

In one aspect, the present invention provides methods of synthesizingdegradable hydroxyl acids blocks, such as the process in Scheme Ia orIb:

In some embodiments, a poly hydroxyl acids oligomer according to Formula(II) is first synthesized according to Huang's methods (U.S. ApplicationNo. 61/054,218) and/or Hermes and Huang's method (U.S. Pat. No.5,349,047), both are herein incorporated by reference in their entirety.Formula (II):

wherein t, m are integers; X is Cl, Br, I, NH₂—, or HO—, R′OCO—C₆H₄—COO—(where R′ is H, CH₃, C₂H₅ or any other alkyls), and R is H, substitutedor unsubstituted alkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedheterocycloalkyl, substituted or unsubstituted aryl and substituted orunsubstituted heteroaryl, substituted or unsubstituted alkoxy, ester,nitro, amine, amide, or thiol.

In some embodiments, R is C₁ to C₁₀ alkyls.

The poly hydroxyl acids oligomer then reacts with ethylene glycol (EG)to form a new oligomer with both ends of halide, hydroxy or amine(Formula (III)) (Scheme I) or with terephthalic acid (TPA) to form a newoligomer with both ends of carboxylic acids or carboxylate esters(Formula (IV)) (Scheme II).

The poly hydroxyl acids oligomer halide then reacts with ethylene glycol(EG) to form a new oligomer with end of hydroxy or which then reactswith terephthalic acid (TPA) to form a new oligomer with both ends ofcarboxylic acids or carboxylate esters (Formula (IV)) (Scheme IIa).

The reaction of oligomer with diol or dicarboxylic acid involved here isesterification reaction which can be accomplished by react carbonylchloride of polyhydroxyl acid oligomers (Formula (V)) with ethyleneglycol or directly react the carboxylic acid group of oligomer toethylene glycol with acid catalysts of ion exchange resin. In the caseof oligomer reacting to terephthalic acid (TPA), it can be accomplishedby reacting TPA with halocarboxylic acid oligomer and amines such astriethylamine or ethyldiisopropylamine.

In some embodiments, the polyhydroxyl acid oligomers have the structureaccording to Formula (V):

wherein t, m are integers; X is Cl, Br, I, NH₂—, or HO—; and R issubstituted or unsubstituted alkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted heterocycloalkyl, substituted or unsubstituted aryl andsubstituted or unsubstituted heteroaryl, substituted or unsubstitutedalkoxy, ester, nitro, amine, amide, or thiol.

In some embodiment, glycol contained degradable blocks (Formula (III))is reacted with TPA or terephthalate according to the Scheme III to formthe blocks with carboxylic acid or carboxylate at both ends (Formula(IIIb):

wherein t, m, n are integers; R′ is H, CH₃, C₂H₅ or any alkyls, R, R₁,R₂ are members independently selected in each structural units from H,substituted or unsubstituted alkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted heterocycloalkyl, substituted or unsubstituted aryl andsubstituted or unsubstituted heteroaryl, substituted or unsubstitutedalkoxy, ester, nitro, amine, amide, or thiol.

(b). Synthesis of Non-Degradable Polymers

The non-degradable blocks, such as polyester (exclude the polyhydroxylacids, which are degradable), polycarbonate or polyamide are synthesizedaccording to methods known in the art. In general, the non-degradableblocks have functional hydroxyl group at the ends of polymer chains(generally with very small amount of carboxylic acid as the end group),which are reactive with degradable short chains.

To control the molecular weight or degree of polymerization ofnon-degradable polymer blocks, the time and pressure of traditionalmelting process can be adjusted. The alternative way is to reactterephthaloyl chloride with diol in various ratio for two differentmonomers to control the degree of polymerization (DP) and the end group(hydroxyl ended or carbonyl chloride ended).

In some embodiment, the non-degradable blocks have the structureaccording to Formula (VI):

wherein n is an integer other than zero, R₁, R₂ and R″ are membersindependently selected in each structural units from H, substituted orunsubstituted alkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedheterocycloalkyl, substituted or unsubstituted aryl and substituted orunsubstituted heteroaryl, substituted or unsubstituted alkoxy, ester,nitro, amine, amide, or thiol.

In some embodiment, the end group of the non-degradable blocks need tobe modified into carboxylic acid, if the blocks will be joined withFormula (III). Scheme IV shows the reaction of the modification:

The solvent used in this reaction is 1,1,2,2-tetrachloroethane or anyother suitable organic solvent which can dissolve the non-degradableblocks at reflux temperature or below.

In case of carbonyl chloride ended blocks, direct hydrolysis convertscarbonyl chloride into carboxylic acid.

(c). Joining Both Degradable Blocks and Non-Degradable Polymers

In another aspect, the present invention provides methods for joiningnon-degradable polymers with degradable blocks together to obtain highmolecular weight polymers.

In conventional polyester manufacturing, copolyesters are typicallyproduced by two different routes: ester exchange plus polycondensation(the DMT process) or direct esterification plus polycondensation (thedirect esterification process). Either of these routes comprises twostages: In the first stage a polymer ester is formed by polymerizationthe monomers at about 180° C. to 230° C. The second stage, referred aspost polymerization reaction, is carried out at a higher temperature(280° C.) or other process to obtain higher molecular weight polyester.

Instead of move on to second stage, the present invention utilizes thedegradable blocks to join the polyesters produced in the first stagedirectly.

In some embodiments, when non-degradable blocks are ended with hydroxylgroup from the melting reaction process, carboxylic acid or carboxylateended degradable blocks (formula IIIA, formula IV) can be added into thereactor of melting process directly at beginning or middle of thereaction. To ensure the degradable blocks are uniformly distributed inthe overall polymer chains, the non-degradable blocks are generallysynthesized first with commercial melting process of polycondensation(e.g. 2-4 hours at 275° C. under vacuum and then the degradable blocksis added and the reaction continues at 275° C. for another 2˜4 hoursunder vacuum.) Scheme V shows one of example reaction in this processwhen the byproduct H₂O is removed under vacuum. Similar ester exchangereactions can be carried out in the melting polymerization by removal ofalcohols under vacuum.

If the distribution of degradable blocks in the final polymer chains isnot a concern, the degradable blocks generally can be added to monomersof non-degradable polymer at the beginning to form degradable blockscontained polymer through mature industrial PET manufacture process,such as those shown in Scheme VI. The distribution of degradable blocksin polymers obtained with such approach will be random but will stilldegradable at their degradable blocks when they are exposed to properenvironments such as basic solution.

In some embodiments, the joint degradable segment is not ended withcarboxylic acid and therefore we need to convert the end groups ofnon-degradable blocks as described herein.

The joining reactions here again are esterification process. Althoughthere are many possible processes to esterification, a very convenientmethod is to follow the reactions between α-halocarboxylate andcarboxylic acid as disclosed in Huang's method (U.S. Patent ApplicationNo. 61/054,218), the disclosure of which is incorporated by reference inits entirety. In order to obtain high molecular weight polymer, thestoichiometry between two reactants, the degradable blocks and shortchain non-degradable polymers with carboxylic acid as end group here,must be controlled very well.

Generally, it is difficulty to calculate the stoichiometry of shortchain non-degradable polymers because of the length diversity of polymerchain. However, due to the acidic end groups in short chain polymers,through titration of the content of acid groups in the polymer solution,we can finger out the acid equivalents per gram and therefore knowexactly how much degradable halo blocks we need to form longerco-polymer.

IV. Applications

The polymers provided herein can find use in a variety of applications,such as packaging bottles for beverages, food packing films, shoppingbags and other containers.

It is understood that the examples and embodiments described herein arefor illustrative purposes only and that various modifications or changesin light thereof will be suggested to persons skilled in the art and areto be included within the spirit and purview of this application andscope of the appended claims. All publications, patents, and patentapplications cited herein are hereby incorporated by reference for allpurposes.

EXAMPLES Example 1

Synthesis of ethylene di-bromoacetylate. To a solution of bromoacetylchloride (TCI, 95 gram, 0.6 mole) in 100 ml dry ethyl acetate was addeddropewisely anhydrous ethylene glycol (Sigma-Aldrich, 12.41 gram, 0.2mole). The solution was stirred at 70° C. under N₂ protection for 16hours and then washed with 200 ml DI water and 200 ml brine. The solventwas removed in vacuum after drying with anhydrous MgSO₄. The crudeproduct was vacuum pumper for 24 hours and then vacuum distilled. ˜100°C./3 mm Hg fraction was collected. 35 gram product was obtained, yield58%. ¹HNMR (CDCl₃, 400 Mz) δ 4.365 (S, 4H); δ 3.830 (S, 4H).

Example 2

Synthesis of ethylene di-bromoacetylate (BrGEGBr). To a 250 ml roundbottom flask were placed bromoacetic acid (Sigma-Aldrich, 69.5 g, 0.5mole), ethylene glycol (Sigma-Aldrich, 15.44 g, 0.25 mole), Dowex C-211,H⁺ form cation ion exchange resin (4 g) and benzene (100 ml). Themixture was refluxed with Dean Stark Trap for 16 hours, record watertrapped. When there was no more water come out, the solution was cooldown to room temperature and the resin was filtrated out. Water wasmeasured (8.5 ml). The solvent benzene was removed in vacuum. Theproduct was vacuum distilled at about 3 mm Hg, ˜100 C/3 mm Hg fractionwas collected (40 g), yield 53%.¹HNMR (CDCl₃, 400 Mz) δ 4.365 (S, 4H); δ3.830 (S, 4H).

Example 3

Synthesis of bromoacetylate glycolic acid (BrGG acid). To a 250 ml roundbottom flask were placed bromoacetic acid (Sigma-Aldrich, 69.5 g, 0.5mole), glycolic acid (Sigma-Aldrich, 37.52 g, 0.5 mole), Dowex C-211, H⁺form cation ion exchange resin (4 g) and benzene (100 ml). The mixturewas refluxed with Dean Stark Trap for 13 hours, record water trapped.When there was no more water come out, the solution is cool down to roomtemperature and the resin is filtrated out. Water was measured (11 ml).The solvent benzene was removed in vacuum. The product was vacuumdistilled at about 3 mm Hg, 105-108° C./3 mm Hg fraction was collected(12.9 g), yield 13.1% (the major product were poly glycolic acidoligomers). ¹HNMR (CDCl₃, 400 Mz) δ 4.850 (S, 2H); δ 3.950 (S, 2H).

Example 4

Synthesis of ethylene bromoacetylate glycolate (BrGGEGGBr). To a 250 mlround bottom flask were placed BrGG acid (from Example III, 29.55 g,0.15 mole), ethylene glycol (Sigma-Aldrich, 7.45 g, 0.12 mole), DowexC-211, form cation ion exchange resin (4 g) and benzene (100 ml). Themixture was refluxed with Dean Stark Trap for 16 hours, record watertrapped. When there was no more water come out, the solution was cooldown to room temperature and the resin was filtrated out. Water wasmeasured (4.3 ml). The filtrate solution is washed with Sat. NaHCO₃ aqsolution (100 ml) to remove excess BrGG. The solvent benzene was removedin vacuum after dried with MgSO4.

Example 5

Synthesis of PET oligomer. To a 250 ml two neck round bottom flaskequipped with condenser are placed terephthalic acid chloride (64.015 g,98%, 0.309 mole) and 150 ml toluene, ethylene glycol (18.658 g, 99.8%,0.3 mole) in 50 ml toluene is dropwisely added at 80° C. (oil bath 100°C.). After completion of addition, the mixture is refluxed under N₂ for16 hours. The solvent is removed in vacuum and the residues are heatedto 120° C. under vacuum for 3 hours. The residues are stirred with H₂O(400 ml) for 3 hours, check pH value shows acidic. The solid product isfiltrated and dried at 120° C. overnight.

Example 6

Synthesis of PET oligomer. To a 250 ml stainless steel bomb are placedBis(2-hydroxyethyl)terephthalate (BHET, Sigma-Aldrich, 30 g, 0.118mole), 350 ppm Sb2O3 (Alfa Aesar) and a magnetic stirring bar. Thesystem is purged with N2/Vacuum three times and then typically heated to275° C. in 30 min. The System is kept at 275° C. under vacuum (3 mm Hg)for a time period from 2˜5 hours. The bomb is then opened and dry ice isadded into the bomb to cool down the melt to room temperature quickly.The bulk solid is roughly grinded into small pieces and the viscosity ismeasured in phenol/1,1,2,2-tetrachloroethane (60/40 weight ratio)according to SPI's (The Society of Plastic Industry) standard PETmeasurement procedure. The Table 1 summarized the IV (intrinsicviscosity) for various reaction times.

Time of Reaction (min) IV 120 0.08 150 0.12 180 0.18 240 0.43

Example 7

Conversion the end group of PET oligomers into carboxylic acid. PEToligomers (IV=0.12, 20 gram from Example 6) is placed in round bottomflask with 1,1,2,2-tetrachloroethane (Alfa Aesar, 100 ml) andTerephthaloyl chloride (sigma-Aldrich, 10 g). The solution is refluxedfor 16 hours with stirring and then is cooled down to room temperatureand diluted with 200 ml ethyl ether. The solid product is collected anddried after filtration, grinded and placed into DI water (400 ml) and150 ml acetonitrile. The mixture is stirred for 5 hours and then pH isadjusted to 7-8 with HCl and stirred for 1 more hour. The white solid iscollected and dried at 120° C. for >3 hours after filtration.

Example 8

Synthesis of PET polymers with GEG blocks. To a solution of PET oligomerfrom Example V (11.088 g, 0.01 mole) and Et3N (2.0238 g, 0.02 mole) in90 ml anhydrous acetonitrile is added dropwisely a solution of BrGEGBr(3.0394 g, 0.01 mole) in 10 ml anhydrous acetoniltrile. The mixture isstirred at room temperature for 48 hours. The solution is poured into500 ml DI water, stirred at room temperature for two hours, filtratedand dried at 110° C. overnight. 11.69 g product is obtained. Yield93.5%.

Example 9

Synthesis of PET polymers with GGEGG blocks. To a solution of PEToligomer from Example 5 (11.088 g, 0.01 mole) and Et3N (2.0238 g, 0.02mole) in 90 ml anhydrous acetonitrile is added dropwisely a solution ofBrGGEGGBr (4.200 g, 0.01 mole) in 10 ml anhydrous acetoniltrile. Themixture is stirred at room temperature for 48 hours. The solution ispoured into 500 ml DI water, stirred at room temperature for two hours,filtrated and dried at 110° C. overnight.

Example 10

Synthesis of PET polymers with degradable blocks. PET oligomers(IV=0.18, 20 gram from Example 6) and degradable blocks (repeat unitmolar ration 10:1) are placed in the stainless steel bomb with amagnetic stirring bar and N2/vacuum purged three times. The system isplaced in a 275° C. oil bath for 3 hours with stirring under vacuum. Thebomb is then opened and added with dry ice to cool down the melt to roomtemperature quickly. The bulk solid is roughly grinded into small piecesand the viscosity is measured in phenol/1,1,2,2-tetrachloroethane (60/40weight ratio) according to SPI's (The Society of Plastic Industry)standard PET measurement procedure. The Table 2 summarized the IV(intrinsic viscosity) for various reaction times.

Example 11

Synthesis of MeGTGMe (Formula (IV)). To a solution of TPA(Sigma-Aldrich, 33.9 g, 98%, 0.2 mole) and Et3N (40.4 g, 56 ml, 0.4mole) in 300 ml anhydrous acetonitrile is added dropwisely a solution ofmethyl bromoacetate (Sigma-Aldrich, 62.44 g, 98%, 0.4 mole) in anhydrousacetonitrile (30 ml). The mixture is stirred at room temperature for 24hours. The solution is then filtrated to remove the solid Et3N salt. Thesolvent in filtrate is removed in vacuum and the residues are washed(stirring in) with 1% HCl (500 ml), NaHCO3 sat aq solution (1000 ml) andwashed with DI water. The white solid product (48.8 g) is collectedafter filtration and drying in oven (120° C.) overnight. Mp=107˜109° C.Yield 78%.

Example 12

Modification of degradable blocks (MeTGEGTMe). To a solution ofmono-Methyl terephthalate (36.03 g, 0.2 mole) and BrGEGBr (30.4 g, 0.1mole) in 150 ml anhydrous acetonitrile is added dropwisely triethylamine(20.24 g, 0.2 mole) in a period of one hour at room temperature. Thesolution was stirred for 20 hours and the white precipitate is filteredout and stirred with 1% HCl (150 ml), NaHCO₃ saturated aqueous solution(150 ml) for two hours respectively. The crude product was collectedthrough filtration and dried at 120° C. overnight. The crude product wasrecrystallized in hot acetonitrile and 37.7 gram final product wascollected, Mp167° C., yield 76%.

Example 13

Synthesis of PET with modified degradable blocks. To a 150 ml roundflask was charged with MeTGEGTMe (14.83 g, 0.03 mole), BHET (7.63 g,0.03 mole) and Sb₂O₃ (0.03 gram). The mixture was heated to 200° C.under vacuum (20 mmHg) with stirring. The melt was kept at 200° C. for 7hours and then poured into ice-water.

Example 14

Synthesis of ethylene glycol capped methyl glycolate. To a solution ofethylene glycol (18.62 g, 0.3 mole), ground NaOH (12 g, 0.3 mole) inanhydrous acetonitrile was added dropwisely methyl chloroacetate (32.56g, 0.3 mole) at 0° C. in a period of 1 hour. The solution was stirred at0° C. for another 7 hours and the solvent acetonitrile was removed invacuum.

Example 15

Synthesis of MeGETEGMe. To a 250 ml round bottom flask were placedterephthalic acid (16.6 g, 0.10 mole), ethylene glycol capped methylglycolate (26.83 g, 0.2 mole), Dowex C-211, H⁺ form cation ion exchangeresin (4 g) and benzene (100 ml). The mixture was refluxed with DeanStark Trap for 16 hours, record water trapped. When there was no morewater come out, the solution was cool down to room temperature and theresin was filtrated out. Water was measured (3.6 ml). The solventbenzene was removed in vacuum. The product was dissolved in ethylacetate and washed with 1% HCl, saturated NaHCO₃ aqueous solution andsaturated NaCl aqueous solution. The solvent was remove in vacuum andthe solid crud product was collected.

Example 16

Polymerization of MeGETEGMe with BHET. Mixture of MeGETEGMe and BHET(1:1 molar ratio) and Sb₂O₃ was melting polymerized according toprevious examples. At the end of polymerization the polymer melt ispoured into the ice-water for quick cooling process.

1. A polymer comprising non-degradable blocks and degradable blocks. 2.The polymer according to claim 1, wherein polymer has a structure ofFormulae (Ia) or (Ib):

wherein t, m, n, p, q are integers other than zero, R, R₁, R₂, R″ aremembers independently selected in each structural units from H,substituted or unsubstituted alkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted heterocycloalkyl, substituted or unsubstituted aryl andsubstituted or unsubstituted heteroaryl, substituted or unsubstitutedalkoxy, ester, nitro, amine, amide, or thiol.
 3. The polymer accordingto claim 2, wherein said R, R₁, R₂, R″ are independently C₁-C₁₀ alkyls.4. The polymer according to claim 1, wherein said degradable blocks hasa structure according to Formula (III)

wherein t, m, n are integers other than zero, X is Cl, Br, I, NH₂—, HO—,R′OCO—C₆H₄—COO— (where R′ is H, CH₃, C₂H₅ or any other alkyls) or otherpolymer chains and R, R₁, R₂ are members independently selected in eachstructural units from H, substituted or unsubstituted alkyl, substitutedor unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heteroaryl,substituted or unsubstituted alkoxy, ester, nitro, amine, amide, orthiol.
 5. The polymer according to claim 1, wherein said degradableblocks has a structure according to Formula (IV):

wherein t, m, n are integers, R is alkyls (CH₃, C₂H₅ . . . ), R″ is anysubstitute groups, and R′ is H or alkyls.
 6. A degradable segmentaccording to Formula (III):

wherein t, m, n are integers other than zero, X is Cl, Br, I, NH₂—, HO—,R′OCO—C₆H₄—COO— (where R′ is H, CH₃, C₂H₅ or any other alkyls), or otherpolymer chains and R, R₁, R₂ are members independently selected in eachstructural units from H, substituted or unsubstituted alkyl, substitutedor unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heteroaryl,substituted or unsubstituted alkoxy, ester, nitro, amine, amide, orthiol.
 7. A degradable segment according to Formula (IV):

wherein t, m, n are integers, R is alkyls (CH₃, C₂H₅ . . . ), R″ is anysubstitute groups, and R′ is H or alkyls.
 8. A method of making apolymer comprising degradable blocks and non-degradable blocks, saidmethod comprises the steps of: (a) synthesizing degradable hydroxylacids blocks; (b) polymerizing non degradable polymer monomer or prepolymer with degradable hydroxyl acids blocks to form said polymers in asolution polymerization process or melting polymerization process.
 9. Amethod of making a polymer comprising degradable blocks andnon-degradable blocks, said method comprises the steps of: (a)synthesizing degradable hydroxyl acids blocks; (b) synthesizingnon-degradable polymers; and (c) joining said non-degradable blocks withand said degradable polymers in a solution polymerization process ormelting polymerization process.
 10. The method according to claim 8 or9, wherein said polymer has the structure according to Formulae (Ia) or(Ib):

wherein t, m, n, p, q are integers other than zero, R, R₁, R₂, R″ aremembers independently selected in each structural units from H,substituted or unsubstituted alkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted heterocycloalkyl, substituted or unsubstituted aryl andsubstituted or unsubstituted heteroaryl, substituted or unsubstitutedalkoxy, ester, nitro, amine, amide, or thiol.
 11. The method accordingto claim 8 or 9, wherein said degradable blocks have the structureaccording to Formula (II):

wherein t, m are integers; X is Cl, Br, I, NH₂—, or HO—, R′OCO—C₆H₄—COO—(where R′ is H, CH₃, C₂H₅ or any other alkyls) and R is H, substitutedor unsubstituted alkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedheterocycloalkyl, substituted or unsubstituted aryl and substituted orunsubstituted heteroaryl, substituted or unsubstituted alkoxy, ester,nitro, amine, amide, or thiol, or Formula (HI):

wherein t, m, n are integers other than zero, X is Cl, Br, I, NH₂—, HO—,R′OCO—C₆H₄—COO— (where R′ is H, CH₃, C₂H₅ or any other alkyls), and R,R₁, R₂ are members independently selected in each structural units fromH, substituted or unsubstituted alkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted heterocycloalkyl, substituted or unsubstituted aryl andsubstituted or unsubstituted heteroaryl, substituted or unsubstitutedalkoxy, ester, nitro, amine, amide, or thiol.
 12. The method accordingto claim 11, wherein said degradable blocks are diol.
 13. The methodaccording to claim 8 or 9, wherein said non-degradable blocks areesters.
 14. The method according to claim 8 or 9, wherein saiddegradable blocks have the structure according to Formula (IV):

wherein t, m, n are integers, X is Cl, Br, I, NH₂—, HO—, R is alkyls(CH₃, C₂H₅ . . . ), R″ is any substitute groups, and R′ is H or alkyls.15. The method according to claim 9, wherein said step (a) is carriedout according to Scheme (Ia):


16. The method according to claim 8 or 9, wherein said step (a) iscarried out according to Scheme (II):

or Scheme (IIa):


17. The method according to claim 8 or 9, wherein said step (c) iscarried out according to Scheme (IV):


18. The method according to claim 10, wherein said degradable andnon-degradable blocks comprise carbonyl chloride ends and said carbonylchloride are converted into carboxylic acid before said step (c).
 19. Amethod of making the degradable segment according to claim 4, saidmethod is carried out according to Scheme Ia:


20. A method of making the degradable segment according to claim 5, saidmethod is carried out according to Scheme Ib:


21. A method of making the degradable segment according to claim 5, saidmethod is carried out according to Scheme Ic: